한빛사논문
Yeonkyoung Park1,2,†, Joori Park1,2,†, Hyun Jung Hwang1,2, Leehyeon Kim2, Kwon Jeong1,2, Hyun Kyu Song2, Simone C. Rufener3, Oliver Muhlemann3 and Yoon Ki Kim1,2,*
1Creative Research Initiatives Center for Molecular Biology of Translation, Korea University, Seoul 02841, Republic of Korea, 2Division of Life Sciences, Korea University, Seoul 02841, Republic of Korea and 3Department of Chemistry and Biochemistry, University of Bern, 3012 Bern, Switzerland
*To whom correspondence should be addressed.
†The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint first authors.
Abstract
Newly synthesized mRNA is translated during its export through the nuclear pore complex, when its 5′-cap structure is still bound by the nuclear cap-binding complex (CBC), a heterodimer of cap-binding protein (CBP) 80 and CBP20. Despite its critical role in mRNA surveillance, the mechanism by which CBC-dependent translation (CT) is regulated remains unknown. Here, we demonstrate that the CT initiation factor (CTIF) is tethered in a translationally incompetent manner to the perinuclear region by the DEAD-box helicase 19B (DDX19B). DDX19B hands over CTIF to CBP80, which is associated with the 5′-cap of a newly exported mRNA. The resulting CBP80–CTIF complex then initiates CT in the perinuclear region. We also show that impeding the interaction between CTIF and DDX19B leads to uncontrolled CT throughout the cytosol, consequently dysregulating nonsense-mediated mRNA decay. Altogether, our data provide molecular evidence supporting the importance of tight control of local translation in the perinuclear region.
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